Multicenter Study on Cardiovascular and Metabolic Complications in Patients With Biochemically Silent Pheochromocytomas and Paragangliomas

The aim of the study is to characterise the cardiovascular and metabolic complications pre- and post-surgery of patients with biochemically negative PPGL and to compare them with normal individuals and patients with secreting PPGLs age and sex matched.

Study Overview

• Status: Enrolling by invitation
• Conditions: Cardiovascular Abnormalities; Diabete Mellitus; Cerebrovascular Disease; Coronary Syndrome; Congestive Heart Failure Chronic; Heart Rate; Arterial Blood Pressure; Hyperlipidaemia; Myocarditis, Pericarditis

Detailed Description

Pheochromocytomas (PHEO) and Paragangliomas (PGL) represent a group of tumors associated with increased cardiometabolic morbidities and mortality. The secretory components of PHEOs/PGLs are well-established risk factors for cardiovascular events and the Endocrine Society Clinical Practice Guidelines have implemented specific instructions for their management and their follow-up. However, data regarding the cardiovascular risk in PHEOs and PGLs asymptomatic patients with the normal biochemical profile are sparse and debating. The incidence of cardiovascular complications and the long-term morbidity in this group of patients is not well-characterized complicating the therapeutic approach or the necessity of pre-operative a-blockade as well as the optimal follow-up, regarding the duration and the need for cardiovascular examination.

Aim Primary outcome v To characterize the cardiovascular and metabolic complications of patients with biochemically negative PPGLs and to compare them with individuals age and sex-matched with normal adrenals (controls) as well as with patients with secreting PHEOs/PGLs.

Secondary outcome v To study also the sub-mentioned parameters post-treatment

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

Study Locations

• Greece
  • Athens, Greece
    • NKUA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Any adult patient with a confirmed histopathological or imaging diagnosis of PPGL (biochemical silent vs secreting)

Description

Inclusion Criteria:

• All PHEOs/PGLs patients should be asymptomatic, with confirmed histopathological analysis for those who had surgery or with positive specific imaging functional studies (MIBG, 68Ga DOTATATE, Octreoscan, Tektrotyde)
• Data about the plasma or urine levels of catecholamines, normetanephrines, metanephrines and methoxytyramine (for PGL) levels should be available for every patient and should be lower than the upper normal values measured with LC-MS (supplementary data about CgA, NSE levels can be also included)
• Available data for the "required" cardiovascular paraclinical or metabolic parameters should be available pre-surgery or at the time of diagnosis or at follow-up for the "not operable" tumors as well as post any treatment

Exclusion Criteria:

• Patients with ambiguous diagnosis of PHEOs/PGLs (absence of histological report and non-specific imaging findings)
• Catecholamines, normetanephrines and metanephrines (and methoxytyramine levels for PGL) levels higher than the upper limit range
• No available data of the required parameters

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Patients with biochemically silent PPGLs; Patients with non-detectable levels of metanephrines/normetanephrines in the blood or in the urine via LC-MS.
Controls ( healthy individuals); Healthy individuals with normal adrenal gland
Patients with secreting PPGLs; Patients with measurable levels of metanephrines or normetanephrines in the blood or urine ( > 2-fold) via LC-MS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in arterial blood pressure (BP) in mmHg before and after any therapeutic intervention	Mean Systolic and diastolic BP (x3) in mmHg before and after any therapeutic intervention or follow-up	Baseline at diagnosis and 6 months post any intervention or follow-up
Changes in the heart rate (pulsation/min) before and after any therapeutic intervention or follow-up	Mean heart rate before and after any therapeutic intervention or follow-up	Baseline at diagnosis and 6 months post any intervention or follow-up
Changes in the fraction of ejection of the heart estimated by cardiac triplex before and after any treatment	Echocardiogram and estimation of fraction of ejection before and after any treatment or follow-up	Baseline at diagnosis and 6 months post any intervention or follow-up
Incidence (number) and characterisation of coronary syndrome (angina, cardiac infarction) before and after any intervention or follow-up	Incidence of an episode of coronary syndrome, like angina or cardiac infarction and evaluation of the electrocardiogram (changes of ST waves or Q waves or Left blovk branch) and signs of ventricule hypokinesia or akinesia in the heart triplex before and after any treatment or follow-up	Baseline at diagnosis and 6 months post any intervention or follow-up
Incidence of cerebrovascular event permanent or transient	Incidence of cerebrovascular disease, permanent or transient, and evaluation with cerebral MRI before and after any therapeutic intervention	Baseline at diagnosis and 6 months post any intervention or follow-up
Incidence of myocarditis before and after any therapeutic intervention	episode of myocarditis based on increased troponine, cardiac MRI and heart triplex before and after any intervention	Baseline at diagnosis and 6 months post any intervention or follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the levels of blood Hb1Ac before and after any therapeutic intervention	Measurement of Hb1AC % in the blood	Baseline at diagnosis and 6 months post any intervention or follow-up
Changes in the concentrations of cholesterol, LDL and HDL in the blood before and after any intervention	Measurement of blood cholesterol in mg/dl, HDL in mg/dl and LDL in mg/dl before and after any therapeutic intervention	Baseline at diagnosis and 6 months post any intervention or follow-up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of the Intima-Media Thickness and of Atheromatous Plaque before and after any intervention	Triplex of carotides with measurement in mm of Intima-Media Thickness and of Atheromatous Plaque (appearance, surface)before and after any intervention	Baseline at diagnosis and 6 months post any intervention or follow-up
Changes of proBNP levels in the blood before and after any intervention	Mesurement of proBNP at blood analysis (pg/ml)	Baseline at diagnosis and 6 months post any intervention or follow-up
Changes in troponine levels in the blood before and after any therapeutic intervention	Measurement of troponine levels (ng/ml) in the blood	Baseline at diagnosis and 6 months post any intervention or follow-up

Collaborators and Investigators

• Sponsor: Laikο General Hospital, Athens

Publications and helpful links

General Publications

• Zhou J, Xuan H, Miao Y, Hu J, Dai Y. Acute cardiac complications and subclinical myocardial injuries associated with pheochromocytoma and paraganglioma. BMC Cardiovasc Disord. 2021 Apr 21;21(1):203. doi: 10.1186/s12872-021-02013-6.
• Kumar A, Pappachan JM, Fernandez CJ. Catecholamine-induced cardiomyopathy: an endocrinologist's perspective. Rev Cardiovasc Med. 2021 Dec 22;22(4):1215-1228. doi: 10.31083/j.rcm2204130.
• Szatko A, Glinicki P, Gietka-Czernel M. Pheochromocytoma/paraganglioma-associated cardiomyopathy. Front Endocrinol (Lausanne). 2023 Jul 13;14:1204851. doi: 10.3389/fendo.2023.1204851. eCollection 2023.
• Y-Hassan S, Falhammar H. Cardiovascular Manifestations and Complications of Pheochromocytomas and Paragangliomas. J Clin Med. 2020 Jul 30;9(8):2435. doi: 10.3390/jcm9082435.
• Constantinescu G, Preda C, Constantinescu V, Siepmann T, Bornstein SR, Lenders JWM, Eisenhofer G, Pamporaki C. Silent pheochromocytoma and paraganglioma: Systematic review and proposed definitions for standardized terminology. Front Endocrinol (Lausanne). 2022 Oct 17;13:1021420. doi: 10.3389/fendo.2022.1021420. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2024
• Primary Completion (Actual): December 1, 2024
• Study Completion (Estimated): February 25, 2027

Study Registration Dates

• First Submitted: December 7, 2025
• First Submitted That Met QC Criteria: December 18, 2025
• First Posted (Actual): January 5, 2026

Study Record Updates

• Last Update Posted (Actual): January 5, 2026
• Last Update Submitted That Met QC Criteria: December 18, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: diabetes; cardiovascular risk; blood pressure; heart rate; pheochromocytoma; paraganglioma; coronary syndrome; cerebrovascular risk; metabiolic syndrome; hypelipidemia
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Endocrine System Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Neoplasms; Heart Diseases; Metabolic Diseases; Neoplasms by Histologic Type; Glucose Metabolism Disorders; Cardiomyopathies; Congenital Abnormalities; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Dyslipidemias; Lipid Metabolism Disorders; Myocardial Ischemia; Chest Pain; Angina Pectoris; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Myocarditis; Diabetes Mellitus; Pheochromocytoma; Paraganglioma; Pericarditis; Cerebrovascular Disorders; Angina, Unstable; Hyperlipidemias; Cardiovascular Abnormalities
• Other Study ID Numbers: 2240/12.02.2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Personal protection data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No